Thromb Haemost 2000; 84(04): 524-527
DOI: 10.1055/s-0037-1614061
Commentary
Schattauer GmbH

Deficiency Causing Mutations and Common Polymorphisms in the Factor XIII-A Gene

L. Muszbek
1   From the Department of Clinical Biochemistry and Molecular Pathology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary
› Author Affiliations
Further Information

Publication History

Publication Date:
11 December 2017 (online)

Summary

Blood coagulation factor XIII (FXIII), for its unique features, used to be considered a stepchild among clotting factors. In contrast to other proenzyme clotting factors, it is the precursor of a transglutaminase and not of a proteolytic enzyme. By cross-linking peptide-bound glutamine and lysine side chains transglutaminases make, rather than break, peptide bonds. Activated FXIII (FXIIIa) cross-links fibrin α-chains and γ-chains and covalently attaches α2-plasmin inhibitor to fibrin α-chains to strengthen fibrin mechanically and to protect it from fibrinolysis. In addition to being a clotting factor, FXIII is also an intracellular proenzyme present in platelets and monocytes/macrophages. The plasma factor is of heterotetrameric structure consisting of two potentially active A (FXIII-A) and two inhibitory/protective B (FXIII-B) subunits (A2B2), while its cellular counterpart is a dimer of FXIII-A. Plasma FXIII is activated by the concerted action of thrombin and Ca2+. Thrombin cleaves FXIII-A at Arg37-Gly38, then in the presence of Ca2+ FXIII-B dissociates and FXIII-A assumes an active configuration (reviewed in ref. 1).

 
  • References

  • 1 Muszbek L, Yee VC, Hevessy Z. Blood coagulation factor XIII: structure and function. Thromb Res 1999; 94: 271-305.
  • 2 Lorand L, Losowsky MS, Miloszevski K. Human factor XIII: fibrin stabilizing factor. Progr Thromb Haemost 1980; 05: 245-89.
  • 3 Board PG, Losowsky MS, Miloszevski KJA. Factor XIII: inherited and acquired deficiency. Blood Reviews 1993; 07: 229-42.
  • 4 Anwar R, Miloszevski KJA. Factor XIII deficiency. Brit J Haematol 1999; 107: 468-84.
  • 5 Seitz R, Duckert F, Lopaciuk S, Muszbek L, Rodeghiero F, Seligsohn U. and Study Group. ETRO Working Party on factor XIII questionnaire on congenital factor XIII deficiency in Europe: Status and perspectives. Sem Thromb Hemost 1996; 22: 415-8.
  • 6 Yee VC, Pedersen LC, Le Trong I, Bishop PD, Stenkamp RE, Teller DC. Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII. Proc Natl Acad Sci USA 1994; 91: 7296-300.
  • 7 Yee VC, Le Trong I, Bishop PD, Pedersen LC, Stenkamp RE, Teller DC. Structure and function studies of factor XIIIA by xray crystallography. Sem Thromb Hemost 1996; 22: 377-84.
  • 8 Weiss MS, Metzner HJ, Hilgenfeld R. Two non-proline cis peptide bonds may be important for factor XIII function. FEBS Lett 1998; 423: 291-6.
  • 9 Anwar R, Gallivan L, Miloszewski KJA, Markham AF. Factor XIII deficiency causing muations. Ser295Arg, in exon 7 of the factor XIIIA Gene. Thromb Haemost 2000; 84: 591-4.
  • 10 Coggan M, Baker R, Miloszevski KJA, Woodfield G, Board P. Mutations causing coagulation-factor-XIII subunit-A deficiency: characterization of the mutant proteins after expression in yeast. Blood 1995; 85: 2455-60.
  • 11 Mikkola H, Muszbek L, Haramura G, Hamalainen E, Jalanko A, Palotie A. Molecular mechanisms of mutations on factor XIII A-subunit deficiency: in vitro expression of in COS cells demonstrates intracellular degradation of the mutant proteins. Thromb Haemost 1997; 77: 1068-72.
  • 12 Takahashi N, Tsukamoto H, Umeyama H, Castaman G, Redeghiero F, Ichinose A. Molecular mechanisms of type II factor XIII deficiency: novel Gly562-Arg mutation and C-terminal truncation of the a subunit cause factor XIII deficiency as characterized in a mammalian expression system. 1998; 91: 2830-8.
  • 13 Kangsadalampai S, Chelvanayagam G, Baker T, Tiedemann K, Kuperan P, Board PG. Identification and characterization of two missense mutations causing factor XIIIA deficiency. Brit J Haematol 1999; 104: 37-43.
  • 14 Mikkola H, Muszbek L, Laiho E, Syrjälä M, Hamalainen E, Haramura G, Salmi T, Peltonen L, Palotie A. Molecular mechanism of a mild phenotype in coagulation factor XIII (FXIII) deficiency: splicing mutation permitting partial correct splicing of FXIII A-subunit mRNA. Blood 1997; 89: 1279-87.
  • 15 Mikkola H, Syrjälä M, Rasi V, Vahtera E, Peltonen L, Palotie A. Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels. Blood 1994; 84: 517-25.
  • 16 Kohler HP, Stickland MH, Ossei-Gerning N, Carter A, Mikkola H, Grant P. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost 1998; 79: 8-13.
  • 17 Wartiovaara U, Perola M, Mikkola H, Tötterman K, Savolainen V, Penttilä A, Grant PJ, Tikkanen MJ, Vartiainen E, Karhunen PJ, Peltonen L, Palotie A. Association of FXIII Val34Leu with decreased risk of myocardial infarction in Finnish males. Atherosclerosis 1999; 142: 295-300.
  • 18 Franco RF, Pazin-Filho A, Tavella MH, Simoes MV, Marin-Neto JA, Zago MA. Factor XIII val34leu and the risk of myocardial infarction. Haematologica 2000; 85: 67-71.
  • 19 Elbaz A, Poirier O, Canaple S, Chédru F, Cambien F, Amarenco P. The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction. Blood 2000; 95: 586-91.
  • 20 Corral J, Gonzales-Conejero R, Iniesta JA, Rivera J, Martinez C, Vicente V. The FXIII Val34Leu polymorphism in venous and arterial thromboembolism. Haematologica 2000; 85: 293-7.
  • 21 Canavay I, Henry M, Morange PE, Tiret L, Poirier O, Ebagosti A, Bory M, Juhan-Vague I. Genetic polymorphisms and coronary artery disease in the South of France. Thromb Haemost 2000; 83: 212-6.
  • 22 Catto AJ, Kohler HP, Coore J, Mansfield MW, Stickland MH, Grant PJ. Association of a common polymorphism in the factor XIII gene with venous thrombosis. Blood 1999; 93: 906-8.
  • 23 Renner W, Koppel H, Hoffmann C, Schallmoser K, Stanger O, Toplak H, Wascher TC, Pilger E. Prothrombin 20210A, factor V Leiden, and FXIII Val34Leu. Common mutations of blood coagulation factors and deep vein thrombosis in Austria 2000; 99: 35-9.
  • 24 Franco RF, Reitsma PH, Lourenco D, Maffei FH, Morelli V, Tavella MH, Araújo AG, Piccinato CE, Zago MA. Factor XIII Val34Leu is a genetic factor involved in the aetiology of venous thrombosis. Thromb Haemost 1999; 81: 676-9.
  • 25 Balogh I, Szöke G, Kárpáti L, Wartiovaara U, Katona É, Komáromi I, Haramura G, Pfliegler G, Mikkola H, Muszbek L. Val34Leu polymorphism of plasma FXIII: biochemistry and epidemiology in familial thrombophilia. Blood 2000; 96: 2479-86.
  • 26 Kangsadalampai S, Board PG. The Val34Leu polymprhism in the A subunit of coagulation factor XIII contributes to the large normal range in activity and demonstrates that the activation peptide plays a role in catalytic activity. Blood 1998; 92: 2766-70.
  • 27 McCormack LJ, Kain K, Catto AJ, Kohler HP, Stickland MH, Grant PJ. Prevalence of FXIII V34L in populations with different cardiovascular risk. Thromb Haemost 1998; 80: 523-4.
  • 28 Kohler HP, Futers TS, Grant PJ. Prevalence of three common polymorphisms in the A-subunit gene of factor XIII in patients with coronary artery disease. Thromb Haemost 1999; 81: 511-5.
  • 29 Attié-Castro FA, Zago MA, Lavinha J, Elion J, Rodriguez-Delfin L, Guerreiro JF, Franco RF. Ethnic heterogeneity of the factor XIII Val34Leu polymorphism. Thromb Haemost 2000; 84: 601-3.
  • 30 Anwar R, Gallivan L, Edmonds SD, Markham AF. Genotype/phenotype correlations for coagulation factor XIII: specific normal polymorphisms are associated with high or low factor XIII specific activity. Blood 1999; 93: 897-905.
  • 31 Suzuki K, Henke J, Iwata M, Henke L, Tsuji H, Fukunaga T, Ishimoto G, Szekelyi M, Ito S. Novel polymorphisms and haplotypes in the human coagulation factor XIII A-subunit gene. Human Genetics 1996; 98: 393-5.
  • 32 Wartiovaara U, Mikkola H, Szöke G, Haramura G, Kárpáti L, Balogh I, Lassila R, Muszbek L, Palotie A. Effect of Val34Leu polymorphism on the activation of the coagulation factor XIII-A. Thromb Haemost 2000; 84: 595-600.
  • 33 Ariens RA, Philippou H, Nagaswami C, Weisel JW, Lane DA, Grant PJ. The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure. Blood 2000; 96: 988-95.
  • 34 Trumbo TA, Maurer MC. Examining thrombin hydrolysis of the factor XIII activation peptide segment leads to a proposol for explaining the cardioprotective effects observed with the factor XIII V34L mutation. J Biol Chem 2000; 275: 20627-31.
  • 35 Kohler HP, Ariëns RAS, Whitaker P, Grant PJ. A common coding polymorphism in the FXIII A-subunit gene (FXIIIVAL34LEU) affects crosslinking activity. Thromb Haemost 1998; 80: 704.
  • 36 Muszbek L, Polgár J, Fésüs L. Kinetic determination of blood coagulation factor XIIII in plasma. Clin Chem 1985; 31: 35-40.
  • 37 Fickenscher K, Aab A, Stüber W. A photometric assay for blood coagulation factor XIII. Thromb Haemost 1991; 65: 535-40.
  • 38 Heins M, Fahron U, Withold W, Rick W. Optimisation of a new continuous UV assay for the determination of blood coagulation factor XIII activity in human plasma. Eur J Clin Chem Clin Biochem 1994; 32: 479-83.
  • 39 Kárpáti L, Penke B, Katona E, Balogh I, Vámosi G, Muszbek L. A modified, optimized kinetic photometric assay for the determination of blood coagulation factor XIII activity in plasma. Clin Chem, in press.;
  • 40 Ariëns RAS, Kohler HP, Mansfield MW, Grant PJ. Subunit antigen and activity levels of blood coagulation factor XIII in healthy individuals. Relation to sex, age, smoking and hypertension. Arterioscler Thromb Vasc Biol 1999; 19: 2012-6.